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Abstract

  1. Top of page
  2. Abstract
  3. Pathophysiology of PAD in CKD Patients
  4. Epidemiology of PAD in CKD Population
  5. Noninvasive Screening Methods
  6. PAD Treatment
  7. Angiography of PAD
  8. Conclusion
  9. References

Peripheral arterial disease (PAD) is a cardiovascular disease risk equivalent and is a common problem in chronic kidney disease patients. Unlike in the general population, PAD in CKD occurs due to medial calcification as opposed to intimal atherosclerotic process. PAD intervention should be performed in select symptomatic patients, as described by the guidelines, and CVD risk factor modification should occur in all CKD patient, regardless of the presence of PAD. As a discipline, Interventional Nephrology has emerged out of a desire to create better outcomes for our patients and to “fix a problem.” The core values of our discipline have evolved out of this fundamental desire to meet an unmet clinical need, to provide insight into a disease state specific to our patients, and to offer clinical/academic excellence in doing so. We must endeavor to follow a similar path in our approach to PAD. The purpose of this review is to educate interventional nephrologists in the diagnosis and treatment of PAD in their CKD patients.

Cardiovascular disease (CVD) is the cause of death in nearly half of end-stage renal disease (ESRD) patients (1). An individual with ESRD has a CVD mortality rate 15 times that found in the general population. Moreover, CVD is the leading cause of death in patients with CKD and a patient with even early stage CKD is 5 to 10 times more likely to die from a cardiovascular event than to progress to ESRD (2). A previous study has shown that peripheral arterial disease (PAD) is associated with a significantly elevated risk of cardiac morbidity and mortality and is generally regarded as a CVD equivalent in terms of mortality risk (3–5). Despite this well-known association, PAD prevalence in the general US population is difficult to pinpoint, treatment is uncertain, and outcomes are poorly defined. This is especially true for the subset of CKD patients with PAD. The purpose of this article is to describe an approach to PAD screening in CKD patients.

Pathophysiology of PAD in CKD Patients

  1. Top of page
  2. Abstract
  3. Pathophysiology of PAD in CKD Patients
  4. Epidemiology of PAD in CKD Population
  5. Noninvasive Screening Methods
  6. PAD Treatment
  7. Angiography of PAD
  8. Conclusion
  9. References

The pathophysiology of vascular disease in the CKD population differs from the nonrenal disease population. Traditional vascular disease comprises intimal disease with lipid-rich plaques producing focal stenoses and the potential for plaque rupture and subsequent thrombosis. In CKD, on the other hand, plaques are characterized by intense medial calcification, which tends toward chronic stenotic disease rather than acute plaque rupture (6). Although medial calcification does occur in the aging population, the form seen in the CKD population occurs at a much earlier age and with much greater severity (7–9).

The most evident factors in the development of medial arterial calcification are serum levels of calcium and phosphate. Relatively early in the progression of CKD, the kidneys retain phosphate. The tissue most exposed to the serum is the vascular endothelium. Recent epidemiologic data suggest that there is a direct correlation between serum phosphate levels and all-cause and cardiovascular mortality in CKD and ESRD (10). Vascular smooth muscle cells (VSMC) also appear central to the process of medial calcification. Vascular smooth muscle cells may undergo trans-differentiation into phenotypically distinct cells that are capable of generating calcification in the presence of inflammation (11).

Epidemiology of PAD in CKD Population

  1. Top of page
  2. Abstract
  3. Pathophysiology of PAD in CKD Patients
  4. Epidemiology of PAD in CKD Population
  5. Noninvasive Screening Methods
  6. PAD Treatment
  7. Angiography of PAD
  8. Conclusion
  9. References

Prior estimates of PAD prevalence in the United States have ranged from 3% to 30% in US adult populations (12–14). A study by Selvin et al. analyzed data from 2174 participants aged 40 years and older from the 1999–2000 National Health and Nutrition Examination Survey (15). PAD was defined as an ankle-brachial index less than 0.90 in either leg. The prevalence of PAD among adults aged 40 years and over in the United States was 4.3%, which corresponds to approximately 5 million individuals. Among those aged 70 years or over, the prevalence was 14.5%. Among the risk factors identified, CKD (OR 2.00, 95% CI 1.08 to 3.70) conferred a two-fold increased risk of PAD. Interestingly, fibrinogen and C-reactive protein levels, which are known to be disproportionately elevated in CKD patients, are also associated with PAD (16).

Most studies of cardiovascular disease in patients with CKD have not examined lower extremity PAD per se (17–19), despite exceedingly high amputation rates in this patient population (20). A study by O’Hare et al. examined the cross-sectional association of PAD, defined as an ankle-brachial index (ABI) <0.9, and CKD stage 3–5, defined as an estimated creatinine clearance (CRCL) <60 mL per min, among 2229 eligible participants in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2000 (21). Univariate logistic regression analysis showed that compared with their counterparts with CKD stage 2 or higher kidney function, patients with moderate-to-severe CKD were at 9-fold increased risk to have an ABI <0.9 (versus an ABI of 1 to 1.3). The authors developed two multivariable models to adjust sequentially for demographic characteristics and comorbid conditions that might confound the association between renal insufficiency and ABI. After adjustment for age, gender, and race, moderate-to-severe CKD remained strongly associated with an ABI <0.9 (OR 3.0, 95% CI 1.7 to 5.3, P<0.001). This association persisted after further adjustment for comorbid conditions including diabetes, coronary artery disease, and history of stroke; measures of diabetes severity (glycosylated hemoglobin, self-reported retinopathy, and insulin use); history of diagnosed hypertension; and measured blood pressure, total cholesterol, BMI, and smoking history. The authors concluded that clinicians should be aware of the remarkably high prevalence of PAD among patients with CKD. Moreover, they argued that accurate identification of patients with CKD combined with routine ABI measurement in this group would greatly enhance efforts to detect subclinical PAD.

Given the increased incidence of PAD in CKD, the K/DOQI guidelines recommend screening all patients upon initiation of dialysis (21). The K/DOQI guidelines, however, in this particular area, must be taken with caution given the weakness in evidence supporting them. In addition, the guidelines address only dialysis patients and do not make specific recommendations for those with CKD. The issue is further complicated by the fact that there is no consensus regarding optimal treatment strategies. The issues regarding cardiovascular mortality, lower limb mortality, patient’s functional status, and candidacy for available medical and interventional therapies must be weighed when making the decision to screen for PAD in CKD. Put simply, patients with CKD and ESRD may not be candidates for revascularization, which would be an argument against screening in these situations in the first place.

Therefore, before screening methods are discussed, it is important to determine risk factors for the presence of PAD. Data from waves 1, 3, and 4 of the United States Renal Data System Dialysis Morbidity and Mortality Study were used to examine cross-sectional associations of a range of conventional cardiovascular risk factors and uremia-related or dialysis-related variables with PAD in a recent study (22). PVD was positively associated with the duration of dialysis (vintage) and malnourished status and was negatively associated with serum albumin and parathyroid hormone levels and predialysis diastolic BP. Kt/V was negatively associated with PVD in waves 3 and 4, but not in wave 1. PVD was associated with increasing age, white (versus non-white) race, male gender, diabetes mellitus, coronary artery disease, cerebrovascular disease, smoking, and left ventricular hypertrophy, as for the general population, but not with hypertension or hyperlipidemia (23).

Noninvasive Screening Methods

  1. Top of page
  2. Abstract
  3. Pathophysiology of PAD in CKD Patients
  4. Epidemiology of PAD in CKD Population
  5. Noninvasive Screening Methods
  6. PAD Treatment
  7. Angiography of PAD
  8. Conclusion
  9. References

Physical Examination and History

Diagnosis begins with a detailed medical history and examination in patients who are at risk for PAD, which, in our patient population, includes all CKD stage 3–5 patients. The medical history should focus on symptoms of claudication, rest pain, impaired ability to walk, and nonhealing lower extremity ulcerations. Claudication, the symptom classically associated with PAD, usually presents as reproducible muscle pain that occurs with activity and improves with rest. It results from a mismatch between oxygen supply to and demand of muscle group during exercise. Conditions other than lower extremity atherosclerosis can result in claudication-like symptoms, such as compartment syndromes, deep venous thrombosis, and spinal stenosis. Therefore, an astute clinician should distinguish between these various diagnoses, looking for signs of trauma, edema, or back problems in addition to PAD. Although claudication is classically associated with PAD, most patients (up to 90%) present with atypical leg symptoms (14,24). At more advanced stages, PAD may manifest as rest pain, nonhealing leg ulcers, or gangrene. Physical examination should focus on skin integrity (e.g., hair loss, presence of wounds or ulcers) and assessment of peripheral pulses with accurate documentation of all pulses at each visit. Diminished bilateral peripheral pulses, femoral bruits, and prolonged capillary refill are very specific for PAD (25).

Noninvasive Testing

Ankle-brachial BP index (ABI) is a simple, noninvasive, and reliable test for PAD screening with a distinct cut-off point for detecting PAD at rest of <0.9 (26). Clinical guidelines for PAD recommend ABI as a screening test for asymptomatic PAD of the lower extremities (27,28). ABI has also been reported to correlate well with PAD severity and angiographic findings (29). One method of measurement uses a 10–12 cm sphygmomanometer cuff placed just above the ankle and a Doppler instrument used to measure the systolic pressure of the posterior tibial and dorsalis pedis arteries of each leg (Fig. 1). These pressures are then divided by the higher brachial pressure of either arm to form the ankle-brachial ratio or “index.” A reduced ABI in symptomatic patients confirms the existence of hemodynamically significant occlusive disease between the heart and the ankle, with a lower ABI (below 0.9) indicating a greater degree of hemodynamic significance of the occlusive disease. The reproducibility of the ABI varies in the literature, but it is significant enough that reporting standards require a change of 0.15 in an isolated measurement for it to be considered clinically relevant, or >0.10 if associated with a change in clinical status. The typical cut-off point for diagnosing PAD is ≤0.90 at rest.

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Figure 1.  ABI calculation.

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In patients with PAD who do not have classic claudication (asymptomatic patients), a reduced ABI is highly associated with cardiovascular events (30). This risk is related to the degree of reduction of the ABI (lower ABI predicts higher risk) and is independent of other standard risk factors. The purpose of screening asymptomatic patients in the general population is to attempt to modify their CVD risk by prescribing aspirin, lipid medications, diet, etc., if they are discovered to have PAD. For this reason, the ABI has become a routine measurement in the primary care practice of medicine (30). In CKD patients, the presence of CKD alone is an independent risk factor for CVD. Thus, by virtue of CKD alone, independent of PAD diagnosis, patients should be treated with an aggressive CVD risk reduction regimen (Fig. 2). For this reason, screening of asymptomatic CKD patients for PAD is not recommended (Tables 1 and 2). For a detailed algorithmic approach to PAD screening in the CKD population, see Fig. 3.

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Figure 2.  Approach to RF modification in the CKD patient with suspected PAD.

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Table 1.   The value of a reduced ABI in the general population differs from that in CKD population
General PopulationCKD
Confirms the diagnosis of PADConfirms the diagnosis of PAD
Detects significant PAD in (sedentary) asymptomatic patientsUsed in the differential diagnosis of leg symptoms to identify a vascular etiology
Used in the differential diagnosis of leg symptoms to identify a vascular etiologyIdentifies patients with reduced limb function (inability to walk defined distances or at usual walking speed)
Identifies patients with reduced limb function (inability to walk defined distances or at usual walking speed) 
Provides key information on long-term prognosis, with an ABI ≤0.90 associated with a 3–6-fold increased risk of cardiovascular mortality 
Provides further risk stratification, with a lower ABI indicating worse prognosis 
Highly associated with coronary and cerebral artery disease can be used for further risk stratification in patients with a Framingham risk score between 10% and 20% 
Table 2.   Recommendations for ankle-brachial index (ABI) screening to detect PAD in the general population and in CKD population
An ABI should be measured in a non-CKD patient:An ABI should be measured in a CKD patient:
 All patients who have exertional leg symptomsAll patients who have exertional leg symptoms
 All patients between the age of 50 and 69 and who have a cardiovascular risk factor (particularly diabetes or smoking) 
 All patients aged ≥70 years regardless of risk-factor status 
 All patients with a Framingham risk score 10–20% 
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Figure 3.  Diagnostic approach to the CKD patient with suspected PAD.

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However, ABI has been suggested as unsuitable for assessing PAD in patients with diabetes, older age, history of intervention for PAD, or advanced CKD (18,31–33). In particular, increased arterial stiffness might interfere with ABI measurements and affect the sensitivity of ABI for detecting PAD among dialysis patients. These patients typically have an ABI >1.40. In some of these patients, the Doppler signal at the ankle cannot be obliterated even at cuff pressures above 300 mmHg (31). In these patients, additional non-invasive diagnostic testing should be performed to evaluate the patient for PAD (Fig. 3).

In an attempt to establish a screening test for PAD that has sufficient diagnostic value and is safe and inexpensive, Ogata et al. attempted to use duplex ultrasound (33). Of the 315 patients evaluated in their study, 23.8% had PAD. The receiver operating characteristic analysis (area under the receiver operating characteristic curve = 0.846) showed that sensitivity and specificity of ABI values for PAD were 49.0% and 94.8%, respectively. As a result of the limitations of ABI and ultrasonographic studies in PAD screening, alternative diagnostic strategies have been employed, including magnetic resonance (MR) angiography and computed tomographic (CT) angiography. While both of these modalities have been shown to be reliably accurate in providing information regarding the presence and extent of vascular disease, they are not without limitations. Alternative tests include toe systolic pressures, pulse volume recordings, transcutaneous oxygen measurements or vascular imaging (most commonly with duplex ultrasound.

Invasive Testing

Unfortunately, CT and MR, once thought to be non-invasive in nature due to their safety profile, are fraught with potential problems for the CKD population. CT uses ionizing radiation and requires the use of iodinated contrast, which is nephrotoxic and could potentially exacerbate CKD. Contrast MR Angiography of the lower extremities is a highly accurate modality, which does not utilize ionizing radiation or iodinated contrast. The emergence of nephrogenic systemic fibrosis (NSF) as a complication of gadolinium use in patients with compromised renal failure has limited the continued use of MRA in the CKD population (34).

As a result, conventional angiography remains the gold standard for diagnosis of PAD in CKD patients with multiple risk factors. Angiography is a highly accurate method for evaluation of PAD. Although invasive, it offers the distinct advantage of allowing for treatment with percutaneous transluminal angioplasty (PTA) or stenting of significant lesions discovered at the time of assessment. The disadvantages of angiography include the use of iodinated contrast and ionizing radiation, relative cost, need for patient sedation and monitoring, and the potential occurrence of associated complications. The potential complications of arterial angiography include bleeding, infection, and vascular injury. Patients with CKD not yet on dialysis, and even those on dialysis in whom residual renal function is an issue, may not be able to safely undergo conventional angiography. However, the use of various preparatory methods prior to angiography seems to diminish the risk of acute kidney injury in the setting of CKD (35). Furthermore, contrast dose can be very strictly managed in these patients by a careful and deliberate approach to diagnostic evaluation in the CKD population (Fig. 3).

PAD Treatment

  1. Top of page
  2. Abstract
  3. Pathophysiology of PAD in CKD Patients
  4. Epidemiology of PAD in CKD Population
  5. Noninvasive Screening Methods
  6. PAD Treatment
  7. Angiography of PAD
  8. Conclusion
  9. References

Treatment of PAD is only indicated if the CKD/ESRD patient exhibits symptoms and signs of claudication, rest pain, impaired ability to walk, or non-healing lower extremity ulcerations. Claudication, the symptom classically associated with PAD, usually presents as reproducible muscle pain that occurs with activity and improves with rest. Claudication results from a mismatch between oxygen supply and demand of muscle groups during exercise. Physical examination should focus on skin integrity (e.g., hair loss, presence of wounds or ulcers) and assessment of peripheral pulses with accurate documentation of all pulses at each visit. Diminished bilateral peripheral pulses, femoral bruits, and prolonged capillary refill are very specific for PAD (27). If a CKD patient complains of the symptoms outlined above and if the suspected diagnosis is corroborated with noninvasive screening tests (ABI <0.9), then treatment should be strongly considered.

Medical Treatment of PAD

The evidence for medical therapies that reduce symptoms and attenuate disease progression is strongest for antiplatelet therapies. There may be a modest benefit with clopidogrel over aspirin as suggested by Clopidogrel versus Aspirin in Patients with Ischemic Events (CAPRIE) trial, which found a reduced cardiovascular risk in the clopidogrel-treated group (36). Although the ACC/AHA guidelines recommend clopidogrel as an aspirin alternative, severe CKD was an exclusion criterion for enrollment in the CAPRIE trial, so the potential benefits of clopidogrel versus aspirin in our patients are unclear (37). However, the Transatlantic Inter-Society Consensus (TASC) guidelines recommend either aspirin or clopidogrel (38). A recent meta-analysis, which evaluated the effects of antiplatelet agents on maximal walking distance (MWD), one of the key parameters of symptom relief in the general PAD population (39), found that the overall pooled estimate was in favor of treatment, but with a modest increase in MWD of 59 m.

Cilostazol and pentoxifylline are phosphodiesterase inhibitors that reduce platelet aggregation and act as a mild vasodilator. Several studies have suggested that cilostazol can reduce claudication and increasing walking times (40–42). Studies with cilostazol showed a significant effect on walking distance at doses of 50 and 100 mg. MWD increased 36 m (95% CI 30–41 m) with 50 mg, but almost twice that, 70 m (95% CI 47–93), with the 100-mg dose (42). It is important to note that the use of cilostazol is contraindicated in patients with congestive heart failure, although there are no studies in this population. In addition, information in the package insert indicates that cilostazol has reduced clearance in severe renal impairment. As his drug has not been studied in dialysis patients, caution is advised for use in individuals with a creatinine clearance <25 ml/minute (42). Pentoxifylline was similarly found to be of modest benefit on MWD (43). Clearance is reduced in renal failure, so dosages must be adjusted appropriately in those settings.

A comprehensive medical therapy algorithm based on the above observations is offered in Fig. 4.

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Figure 4.  Medical treatment algorithm for PAD in CKD patients.

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Angiography of PAD

  1. Top of page
  2. Abstract
  3. Pathophysiology of PAD in CKD Patients
  4. Epidemiology of PAD in CKD Population
  5. Noninvasive Screening Methods
  6. PAD Treatment
  7. Angiography of PAD
  8. Conclusion
  9. References

Severe forms of PAD often manifest as the clinical entity known as critical limb ischemia, which is defined by rest pain and ischemic skin lesions, such as ulcers and gangrene. In the general population, revascularization is the optimal therapy for critical limb ischemia (21,44). Revascularization via PTA procedures is preferred to surgical revision in most cases. There are no randomized, controlled trial data regarding revascularization techniques in patients with CKD and dialysis patients, however. Not surprisingly, a retrospective analysis of patients who had CKD and underwent lower limb revascularization found lower rates of limb loss and mortality compared with ESRD (44). What is more, mortality rates were found to be inversely correlated with kidney function (45). Patients with ESRD often are not good candidates for PTA because of distal disease and vascular calcifications. Nevertheless, a retrospective analysis of hemodialysis patients saw lower mortality and higher limb salvage rates in those who underwent percutaneous revascularization compared with a surgical approach (46).

Once a patient is judged to be a likely candidate to benefit from intervention, an angiogram is scheduled. Contrast angiography remains the gold standard for diagnosis and the assessment of the severity of atherosclerotic PAD. The value of this diagnostic modality has been buoyed by the recently described association of Nephrogenic Systemic Fibrosis (NSF) with magnetic resonance contrast agents, such as are required for MR angiography (47). Angiography, furthermore, allows evaluation of the abdominal aorta, renal arteries and branch vessels, the presence of accessory renal arteries, as well as cortical blood flow and renal dimensions (48). Moreover, pressure gradients across arterial lesions can be obtained to evaluate its hemodynamic significance of said lesions if the angiographic or noninvasive testing data are equivocal. Digital subtraction angiography (DSA) has become available in many institutions and, although its resolution is inferior to film, it permits the use of lower concentrations of iodinated contrast, as well as of alternative contrast agents such as CO2 (49).

The disadvantages of angiography include the use of iodinated contrast and ionizing radiation, relative cost, need for patient sedation and monitoring, and the potential occurrence of associated complications. The potential complications of arterial angiography include bleeding, infection, cholesterol embolization, and vascular injury. Patients with CKD not yet on dialysis, and even those on dialysis in whom residual renal function is an issue, may not be able to safely undergo conventional angiography. However, the use of various preparatory methods prior to angiography seems to diminish the risk of acute kidney injury in the setting of CKD (37). Furthermore, contrast dose can be very strictly managed in these patients by a careful and deliberate approach to diagnostic evaluation in the CKD population.

Typically, an abdominal aortogram is performed with distal runoff, usually positioning a pigtail catheter at the lower edge of the first lumbar vertebra and power-injecting 20–40 ml of dye at 20 ml/second. The abdominal aortogram will provide information regarding the aorta itself, the position of the renal arteries, and the presence of iliac calcification. Runoff into the lower extremities must be done properly by moving the image intensifier or table such that the flow of contrast can be followed. This takes a certain degree of experience and can lead to repeated aortograms if not performed properly. In most instances, the aortogram provides adequate visualization of the peripheral arterial tree, but if optimal imaging or pressure gradient measurement is needed, selective catheterization becomes necessary. This can be achieved with a variety of different 4–6 F diagnostic catheters. Whatever catheter shape is used, the goal is to achieve selective cannulation of the artery in question without excessive catheter manipulation, as atheromas are often adjacent to areas of disease, and distal embolization can occur (48).

The arterial supply of the lower extremities begins with aortic bifurcation into the ileofemoral system. The common iliac artery continues into the internal and external iliac artery, and, from the external iliac, to the common femoral artery. The common femoral artery gives origin to the superficial epigastric artery, the external pudendal and the superficial circumflex arteries, and subsequently bifurcates into the profunda femoris and superficial femoral arteries (SFA). The profunda femoris gives rise to the medial and lateral circumflex femoral arteries, and to perforating arteries supplying the thigh muscles. Importantly, the profunda femoris can provide substantial collateral flow when the superficial femoral artery is occluded, via branches to the lateral geniculate artery, which in turn supplies the above-the-knee popliteal artery.

The SFA has few side branches and distally enters the adductor canal to form the popliteal artery. A descending medial geniculate branch can originate from the distal SFA proximal to the adductor canal, and can provide additional collateralization distally to the knee. The below-the-knee popliteal artery branches into the anterior tibial artery and the tibioperoneal trunk. The anterior tibial artery becomes the dorsalis pedis artery at the level of the ankle, whereas the tibioperoneal trunk divides into the peroneal and posterior tibial arteries, which eventually form the medial and lateral plantar arches. The dorsalis pedis ends in the dorsal arch, which communicates with the plantar arch via perforating branches, and gives origin to the dorsal metatarsal arteries. The plantar arch gives origin to the metatarsal and plantar digital arteries.

Different strategies to visualize the lower extremities can be applied, depending on the available angiographic equipment. With a large field of view, both lower extremities can be visualized at the same time. In this case, a pigtail catheter can be positioned at the aorto-iliac bifurcation, and angiography can be performed with 80 cc of dye injected at a rate of 10 cc per second using stepped digital subtraction views.

Alternatively, unilateral lower extremity angiograms can be performed by crossing over the bifurcation into the contralateral common iliac artery with a straight tip catheter over a floppy wire. In this case, stepped manual or automated DSA injections can be performed, sometime even with partially diluted contrast. With digital subtraction imaging, it is important that the patient remain still, thus ensuring patient collaboration an important consideration when administering sedation. Upon withdrawal of the catheter into the ipsilateral common iliac, an angiogram of the remaining limb can be performed in a similar fashion. The latter imaging method is preferred for CKD patients as a means of minimizing contrast exposure.

Interventional approach

Percutaneous intervention on PAD in CKD patients should be considered only if one of the following conditions is met:

  • 1
     Symptomatic and refractory to medical therapy
  • 2
     Critical limb ischemia is present

Medical therapy of the CKD patient with claudication is described above. If the CKD patient has been treated with medical therapy with no improvement in symptoms, then percutaneous revascularization may be considered (Fig. 4). Critical limb ischemia (CLI) is different from claudication per se, and can be defined as limb pain that occurs at rest or impending limb loss that is caused by severe compromise of blood flow to the affected extremity. All CKD patients with rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease should be categorized as CLI. Unlike individuals with claudication, patients with CLI have resting perfusion that is inadequate to sustain viability in the tissue bed and which frequently leads to amputation (Fig. 5). Therefore, CLI should be considered for percutaneous revascularization at the same time that medical therapy is initiated (30).

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Figure 5.  Natural history of PAD in non-CKD patients.

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Claudication and CLI exist on a continuum, which makes it challenging to simplify this complex disease state into two distinct categories. For this reason, guidelines have been developed to subcategorize PAD into several distinct subtypes based on characteristics of lesion morphology (43). These classifications are summarized in Tables 3 and 4 for supra- and infra-inguinal disease, respectively. The symptoms that a given lesion is causing can also be divided into stages (Table 5) (30). Based on classification of symptoms and lesion morphology, the interventional plan can then be determined based on the algorithms described in Figs 6 and 7).

Table 3.   TASC stratification of supra-inguinal lesions
Type A lesions
 Single stenosis less than 3 cm of the CIA or EIA (unilateral/bilateral)
Type B lesions
 Single stenosis 3–10 cm in length, not extending into the CFA
 Total of 2 stenoses less than 5 cm long in the CIA and/or EIA and not extending into the CFA
 Unilateral CIA occlusion
Type C lesions
 Bilateral 5- to 10-cm-long stenosis of the CIA and/or EIA, not extending into the CFA
 Unilateral EIA occlusion not extending into the CFA
 Unilateral EIA stenosis extending into the CFA
 Bilateral CIA occlusion
Type D lesions
 Diffuse, multiple unilateral stenoses involving the CIA, EIA, and CFA (usually more than 10 cm long)
 Unilateral occlusion involving both the CIA and EIA
 Bilateral EIA occlusions
 Diffuse disease involving the aorta and both iliac arteries
 Iliac stenoses in a patient with an abdominal aortic aneurysm or other lesion requiring aortic or iliac surgery
Table 4.   TASC stratification of infra-inguinal lesions
Type A lesions
 Single stenosis less than 3 cm of the superficial femoral artery or popliteal artery
Type B lesions
 Single stenosis 3–10 cm in length, not involving the distal popliteal artery
 Heavily calcified stenoses up to 3 cm in length
 Multiple lesions, each less than 3 cm (stenoses or occlusions)
 Single or multiple lesions in the absence of continuous tibial runoff to improve inflow for distal surgical bypass
Type C lesions
 Single stenosis or occlusion longer than 5 cm
 Multiple stenoses or occlusions, each 3–5 cm in length, with or without heavy calcification
Type D lesions
 Complete common femoral artery or superficial femoral artery occlusions or complete popliteal and proximal trifurcation occlusions
Table 5.   Rutherford classification of PAD symptoms
CategoryClinical description
0Asymptomatic
1Mild claudication
2Moderate claudication
3Severe claudication
4Ischemic rest pain
5Minor tissue loss
6Ulceration or gangrene
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Figure 6.  Supra-Inguinal lesion treatment algorithm.

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Figure 7.  Infra-Inguinal lesion treatment algorithm.

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The importance of arterial access in percutaneous interventions of the lower extremities cannot be overemphasized. Access location depends on a variety of considerations, including lesion location, catheters, balloons and stents shaft length, and the quality of the arterial pulsation at the selected site. In general, for common and proximal external iliac artery stenosis, the retrograde ipsilateral approach through a short introducer sheath is recommended. For the distal external artery, internal iliac and common femoral artery, the contralateral retrograde approach through a long sheath is preferred. The proximal two-thirds of the superficial femoral artery can also be easily treated through this approach, but for challenging distal lesions, and especially for occluded or diffusely diseased popliteal and tibioperoneal arteries, the antegrade ipsilateral approach often allows more direct and coaxial manipulation of wires and balloons. A 5 to 6 Fr sheath is sufficient for most balloon catheters used for interventions in the lower extremities, but 6 to 7 Fr sheaths might work better when stent deployment is necessary. Careful planning of the procedure, along with familiarity with available equipment, will typically minimize the amount of sheath exchanges and expedite the procedure.

For most iliac and femoral lesions, an 0.035-inch wire is usually sufficient. For long stenoses or chronic total occlusions (Fig. 8), hydrophilic wires and catheters are typically used instead. When a chronic total occlusion (CTO) is particularly challenging, coronary balloons with dedicated 0.014-inch CTO wires can be used. The choice of balloon lengths and diameters changes with the lesion treated, and in general, it is best to start with undersized balloons to minimize the risk of dissection or perforation. Typically, the final balloon size will be in the 8–10 mm range for the common iliac artery, 6–8 mm for the external iliac, 5–6 mm for the common femoral artery, 4–6 mm for the superficial femoral artery, and 4–5 mm for the popliteal artery. For the tibio-peroneal vessels, coronary balloons <4 mm in diameter are often used.

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Figure 8.  SFA disease before and after intervention – (A) Chronic total occlusion of SFA with collateral flow. (B) Extraluminal wire. (C) Angioplasty. (D) Dissection. (E) Poststent placement. (F) Improved flow to distal lower extremity.

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Stent selection also depends on arterial size and location of the target lesion; the latter will also influence what type of stent will be used, namely balloon or self-expandable. In general, aorto-ostial lesions such as the aorto-iliac bifurcation are best treated with balloon expandable stent (in most cases, implanted with the “kissing” technique [Fig. 9]). Self-expandable nitinol stents are used for external iliac, common femoral, and superficial femoral arteries. Whether to use stents routinely for superficial femoral arteries, or for popliteal and tibio-peroneal vessels, remains a matter of ongoing debate. A detailed description of atherectomy catheters or specialized CTO devices is beyond the scope of this review.

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Figure 9.  Aorto-iliac bifurcation intervention using bilateral retrograde approach and “kissing” technique.

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Precautions

Careful attention to contrast dye load is required, especially in patients at high risk for contrast nephropathy. As mentioned above, CO2 can be used as alternative contrast agents at least during some parts of the intervention.

Adjuvant pharmacology before and after peripheral percutaneous intervention has not been systematically studied. Heparin to maintain an ACT of 250–300 seconds is frequently used as the anticoagulant of choice during interventional procedures; most interventionalists are quite familiar with its use and it can be easily reversed with protamine. Patients are usually pretreated with aspirin, which is continued indefinitely. The use of clopidogrel seems theoretically necessary following percutaneous intervention; however, there are no controlled studies exploring its use CKD patients with PAD. However, if the CKD patient has symptoms of PAD justifying intervention, they should be treated with clopidogrel by virtue of that alone. Other possible intraprocedural anticoagulants, such as glycoprotein 2B3A receptor antagonists and direct thrombin inhibitors such as bilvalrudin have not been formally studied in peripheral interventions in CKD.

PAD intervention requires close attention to several important details that are typically not a major concern in the venous system. When performing arterial intervention, one must not oversize the balloon or undersize the stent (48). In addition, there is no reason to use a longer balloon than you need and one should aim for 5 mm extension beyond the length of the lesion when selecting balloon length. The guide wire should be kept across the lesion at all times, even when retracting the balloon in what one feels is a successful intervention. One should seldom intervene before giving anticoagulation. One should not inflate an angioplasty balloon over nominal pressure in the arterial system, as balloon rupture can lead to acute limb ischemia in the arterial system. A partially inflated balloon should not be retracted and it is best to intervene in the arterial system with a sheath that engages the lesion in question (48). Most importantly, one must not allow air into the arterial system, especially when operating on the great vessels of the thoracic aorta. In most cases, a manifold can be used to minimize the probability of air embolization.

Given the above precautions, PAD intervention should be performed only by skilled interventionalists who are specifically trained for PAD intervention. These practitioners should have a thorough knowledge of the medical/cognitive components of the decision-making process as described above. To date, there is no entity that trains, certifies, or accredits Nephrologists in this discipline. Furthermore, the procedures described above should only be performed if there is adequate monitoring and surgical backup to allow detection and treatment of the potential complications of PAD intervention, including, but not limited to, acute limb ischemia, arterial thrombosis, arterial dissection, etc.

Conclusion

  1. Top of page
  2. Abstract
  3. Pathophysiology of PAD in CKD Patients
  4. Epidemiology of PAD in CKD Population
  5. Noninvasive Screening Methods
  6. PAD Treatment
  7. Angiography of PAD
  8. Conclusion
  9. References

PAD is a problem that affects CKD patients out of proportion to the general population and mirrors CVD outcomes very closely. Unlike the general population, PAD in CKD occurs due to medial calcification as opposed to an intimal atherosclerotic process. PAD intervention should be performed in select symptomatic patients, as described by the guidelines, and CVD risk factor modification should occur in all CKD patient, regardless of the presence of PAD.

As a discipline, Interventional Nephrology has emerged out of a desire to create better outcomes for our patients and to “fix a problem.” The core values of our discipline have evolved out of this fundamental desire to meet an unmet clinical need, to provide insight into a disease state specific to our patients, and to offer clinical/academic excellence in doing so. We must endeavor to follow a similar path in our approach to PAD.

References

  1. Top of page
  2. Abstract
  3. Pathophysiology of PAD in CKD Patients
  4. Epidemiology of PAD in CKD Population
  5. Noninvasive Screening Methods
  6. PAD Treatment
  7. Angiography of PAD
  8. Conclusion
  9. References
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